Human papillomavirus (HPV) is a sexually transmitted infection and primary cause of anal cancer. While male anal cancer incidence in the US has increased almost threefold in three decades, anal HPV prevalence and risk factors in men, especially heterosexual men, remain largely unknown. We have recently estimated an anal canal HPV prevalence of 16.6% in 222 men who denied any lifetime sex with another man. In our analysis of these data, we also found significant univariate associations between anal HPV and decreased age, increased lifetime number of female sexual partners, and frequency of sexual intercourse in the previous month. In multivariate analysis, number of lifetime sexual partners and frequency of sex was independently associated with anal HPV. Our long term goal is to increase our understanding of anal HPV in heterosexual men so that prevention approaches such as vaccination can be developed and implemented to reduce anal cancer burden. The focus of this application is to determine the prevalence and risk factors for anal HPV in heterosexual men. Our hypothesis is that anal HPV in heterosexual men is a common infection inversely associated with age. This hypothesis can be efficiently tested given the availability of anal canal specimens from a large multinational study conducted by our collaborators at the H. Lee Moffitt Cancer Center. Dr. Anna Giuliano and colleagues have collected and archived anal canal samples from 1200 men recruited in Tampa, Florida;Morelos state, Mexico;and Sao Paulo, Brazil. We propose to test these anal canal samples for HPV. The specific aims of this cross-sectional study are designed to exploit the availability of the anal canal specimens from the larger study of 1200 men: Specific Aim 1. Using archived anal canal samples, determine the type-specific anal HPV prevalence in 1200 men;and Specific Aim 2. Identify factors independently associated with anal HPV in the 1200 men. HPV is a common sexually transmitted infection responsible for a variety of anogenital cancers including anal cancers in men. However, a high anal HPV prevalence in heterosexual men, if confirmed, will challenge assumptions about the epidemiology of HPV in men. The dramatically increased incidence of anal cancers in men in the last three decades underscores the need to learn more about prevalence of anal HPV in men (Specific Aim 1) and the risk factors most commonly associated with anal HPV in these men (Specific Aim 2). The focus of this application is to determine the prevalence and risk factors for anal HPV in 1200 heterosexual men. Our hypothesis is that anal HPV in heterosexual men is a common infection inversely associated with age.